1. 1. WHAT YOU SHOULD HAVE READ BUT.2010
   • asthma
   University of Verona, Italy Attilio Boner
2. 2. Asthma phenotypes
3. 3. Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling HollamsJACI 2009;124:463
   • 1380 unselected14-year-olds.
   • Clinical history, allergic sensitization, and respiratory function.
   % SUBJECTS 60% 60 50 40 30 20 10 0 ATOPIC ASTHMATIC 10%
4. 4. Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling HollamsJACI 2009;124:463
   • 1380 unselected14-year-olds.
   • Clinical history, allergic sensitization, and respiratory function.
   % SUBJECTS 60% 60 50 40 30 20 10 0 ATOPIC ASTHMATIC 10% 81% of asthmatic subjects were also atopic.
5. 5. Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling HollamsJACI 2009;124:463
   • 1380 unselected14-year-olds.
   • Clinical history, allergic sensitization, and respiratory and immunoinflammatory function.
   % SUBJECTS 60% 60 50 40 30 20 10 0 ATOPIC ASTHMATIC 10% 81% of asthmatic subjects were also atopic.BHR was associated strongly with atopic but not with nonatopic asthma,andthe BHR risk profile was itself dominated byatopy-associated variables.
6. 6. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program MooreAJRCCM2010;181:315
   • Severe Asthma Research Program cohort.
   • Cluster analysiswas performedon 726 subjects.
   5 groups were identified.Subjects in Cluster 1 (n=110) haveearly onset atopic asthmawith normal lung functiontreated with two or fewer controller medications(82%) and minimal health care utilization. Cluster 2(n=321)consists of subjects withearly-onset atopic asthmaand preserved lung function butincreased medication requirements (29% on three or more medications) and health care utilization.
7. 7. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program MooreAJRCCM2010;181:315
   • Severe Asthma Research Program cohort.
   • Cluster analysiswas performedon 726 subjects.
   Cluster 3 (n=59) is a unique group of mostlyolder obese womenwith late-onset nonatopic asthma, moderate reductions in FEV 1 , and frequent oral corticosteroid use to manage exacerbations.Subjects in Clusters 4 (n=120) and 5 (n=116) havesevere airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids.
8. 8. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program MooreAJRCCM2010;181:315Using three variables (baseline FEV 1[with a bronchodilator withhold], maximal "Max" FEV 1after six to eight puffs of albuterol, and age of onset of asthma), subjects can be assigned to the five clusters that range from milder asthma(Cluster 1) to more severe disease (Clusters 4 and 5).
9. 9. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program MooreAJRCCM2010;181:31550 40 30 20 10 0 5 0 % Sputum:Eosinophils ,Neutrophils 12345 23.3% 33.3% 37.6% 34.7% 48.3% 0.7% 0.7% 1.9% 1.5% 1.2% Cluster
10. 10.
    • asthma natural history
11. 11. Background:Clinicians have difficulty indiagnosing asthma in preschool children withsuggestive symptoms. Objective:We sought to develop a clinical asthmaprediction score for preschool children who haveasthma-like symptoms for the first time. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age CaudriJACI 2009;124:903
12. 12. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age CaudriJACI 2009;124:903
    • Birth cohort followed3,963 children for 8 years .
    • Between 0 and 4 years of age, 2,171 (55%) children reported wheezing, coughing at night withouta cold, or both.
    • Asthma was defined as wheezing, inhaled steroid prescription, or a doctor's diagnosis of asthma at both age 7 and 8 years of age.
    % Children with Symptoms at 0 to 4 Years of Age 11% HAD ASTHMA at 7 to 8 YEARS 11 10 9 8 7 6 5 4 3 2 1 0
13. 13. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age CaudriJACI 2009;124:903
    • Male sex,
    • Post-term delivery,
    • Parental education
    • Inhaled medication,
    • Wheezing frequency,
    • Wheeze/dyspnea apart from colds,
    • Respiratory infections,
    • Eczema
    8 clinical parametersindependentlypredicted asthmaat 7 to 8 years of age:
14. 14. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age CaudriJACI 2009;124:903 MALE SEX 2.5 2.0 1.5 1.0 0.5 01.7 POST-TERM DELIVERY MEDIUM/LOW PARENTAL EDUCATION ECZEMA 3 4 2.5 1.5 2.1 1.5 2.3 ORFOR ASTHMA AT AGE 7-8 YEARS WHEEZINGFREQUENCY TIMES/Y
15. 15. Increased Fraction of Exhaled Nitric Oxide Predicts New-Onset Wheeze in a General Population Olin AJRCCM2010;181:32449 subjects reported new-onset wheeze
    • 2,200 men and women from a general populationbased study.
    • Questionnaires, blood samples, pulmonary function tests, and F E NO.
    • Follow-up 4 years later.
16. 16. 18.8 New-onset No onset 20 15 10 0 5 015.8 Increased Fraction of Exhaled Nitric Oxide Predicts New-Onset Wheeze in a General Population Olin AJRCCM2010;181:324Median Concentrationof FeNO at Baseline ppb p=0.03
    • 2,200 men and women from a general populationbased study.
    • Questionnaires, blood samples, pulmonary function tests, and F E NO.
    • Follow-up 4 years later.
    Wheeze
17. 17. 2.8 90 percentile 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 03.2
    • 2,200 men and women from a general populationbased study.
    • Questionnaires, blood samples, pulmonary function tests, and F E NO.
    • Follow-up 4 years later.
    Increased Fraction of Exhaled Nitric Oxide Predicts New-Onset Wheeze in a General Population Olin AJRCCM2010;181:324ORfor new-onset wheeze 95 percentile Baseline FeNO
18. 18. Adulthood asthma after wheezing in infancy:a questionnaire study at 27 years of age M. Ruotsalainen, Allergy 2010;65;503
    • At the median age of 27.3 years
    • questionnaire to 59 study subjects hospitalized for wheezing at